Naked Mole Rat: Freak of Nature

A frequent entry in ‘Top 10 Ugliest Animal’ lists, the naked mole rat truly is a sight to behold. A cross between, a mole and a rat, with a sprinkle of naked has produced a physical abomination. Despite its looks, the naked mole rat has remarkable physiology and is one of the most interesting animals, biologically speaking, ever discovered.

From insensitivity to pain, to powerful cancer resistance, the naked mole rat has intrigued scientists the world over for attributes not found in other mammals. Studying the perplexing physiology of these animals may unlock new therapeutic avenues for the treatment of human disease, cancer being the most relevant.

The naked mole rat is a burrowing animal and described as ‘eusocial’ – this is considered the highest level of organisation in animal society and involves things like co-operative brood care (all mothers looking after all infants collectively) and organised division of labour. Hive animals such as ants and termites are considered eusocial but only two known eusocial mammals have been reported, including the naked mole rat.

The naked mole rat lives in unusually harsh conditions which is thought to be the main driving force behind their strange physiological adaptions. They live primarily in arid African deserts . Groups of about 80 individuals reside in complex underground burrow systems. Like hive insects, naked mole rats have a ‘queen’ female who produces young which are tended to by non-breeding females. ‘Worker’ animals serve to defend the hive from attack, acquire food and maintain/dig the tunnel systems. It’s all pretty mad that this set-up exists in a mammal as this sort of system is very much associated with insects.

However, their social layout is just the tip of the iceberg when it comes to these remarkable creatures. Lets take a look at why the naked mole rat is a ‘medical marvel’.

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#1 Pain Insensitivity

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This can be explained, from a biological standpoint, rather simply. We know that naked mole rats lack a key neurotransmitter in the skin called Substance P which in ‘normal’ mammals is very important in transmitting pain signals to the central nervous system (1).

In an interesting experiment, it was shown that if Substance P is injected into the naked mole rats, they once again feel pain but NOT to acids. So the system to feel pain in the skin exists but they have evolved to lack a key component and also cannot feel acid-induced pain even when this key component is reintroduced (2). So we know why, on a cellular level they don’t feel pain but what about why this evolved in the first place?

Due to where they live the leading theory is that this lack of substance P is to combat pain from acid build up in tissues which results from living in cramped poorly oxygenated spaces with high levels of carbon dioxide.

They have other adaptions which fit with this low oxygen environment including possessing blood with an extremely high affinity for oxygen as well as a very low respiratory and metabolic rates. They consume a fraction of the energy of a similarly sized rat (3).

Crazy stuff and a remarkably specific adaption to the environment.

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#2 Resistance To Cancer

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Naked mole rats are highly resistant to tumours (4) but can still suffer from related disorders – in 2016 two individuals born and raised in captivity were shown to have developed tumours for the first time, so it is possible. Bear in mind, these animals are living in a much more oxygen rich environment that they do in the wild which may have promoted tumour growth (5).

Studies have revealed the exact cellular mechanisms by which naked mole rats are resistance to cancers. Whereas most mammals, including us, have one major genetic defence against tumours, naked mole rats possess two.

Gene p 27 is an ‘over-crowding gene’ that prevents cell division once individual cells make contact with one another. This is known as contact inhibition. We all posses this gene. Another similar gene called p 16 which functions in a similar manner is used by naked mole rats alongside p 27 acting as a double barrier to uncontrolled cellular proliferation. If their version of p 27 is mutated and ceases to function, p 16 can fulfil this role alone (6). We however are not so lucky.

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What even is this?

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More recent evidence suggests that the naked mole rats produce a unique version of a compound that we mammals share but which acts as a kind of anti-cancer agent (7). Surprisingly the same compound which gives them stretchy skin may also be why they are so cancer resistance. Hyaluronan is a component of connective tissue found across all mammals. Naked mole rats have a particularly long version of this molecule. Removing this molecule from cultured mole rat cells increases cancer rates massively. This compound is thought to be key in why naked mole rat cells have much more sensitive cellular contact inhibition in comparison to humans

Work is currently being undertaken to work out how we would potentially apply this to human cancer treatments.

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#3 Thermoregulation

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Another bizarre trait. Naked mole rats do not regulate their body temperature like other mammals. They are described as ‘thermoconformers’ whereas mammals in general are ‘thermoregualtors’ (8) . Most mammals maintain a constant internal body temperature regardless of ambient temperature. However, naked mole rats body temperature tracks ambient temperature, more like a reptile. Naked mole rats have been shown to make great use of behavioural thermoregulation.

When cold, they huddle together in shallower parts of their tunnels to absorb heat from the sun, when too warm, they retreat to deeper and cooler parts of their homes (9).

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#4 Long Life Span

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Not only do naked mole rats not get cancer and not feel pain but they also live for bloody ages, You guessed it. They are hell spawn.

For their size they live for absolutely ages – up to 31 years (!). The general rule of thumb is the smaller the animal the shorter the life span. Not true of the mole rat. Naked mole rats live up to 10 times longer than a rat (and at 3 years, that rat would be ancient). The exact reasons for why they live so long aren’t fully understood but a number of plausible physiological adaptions may explain it.

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As already discussed, they are highly resistance to cancer, something which plagues male rats (10)

They maintain healthy vascular function well into their old age and do so much better than other rodents (11)

They can reduce metabolic rate during hard times which may help them avoid age-induced damage from oxidative stress(12)

DNA repair pathway genes expressed much more highly then short lived rodents: better DNA repair may facilitate greater longevity and does fit with the well known ‘DNA damage theory of aging’ (13,14)

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True freaks of nature but ones which hold therapeutically valuable information regarding cellular mechanisms of cancer resistance. Don’t judge a book by its cover. Naked mole rats are ugly bastards but one day you may owe your life to research successfully carried out on these little ball bags.